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Stem Cell Research & Therapy Apr 2023Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn's Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future.
SHORT CONCLUSION
MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs' efficacy.
Topics: Humans; Quality of Life; Mesenchymal Stem Cell Transplantation; Treatment Outcome; Mesenchymal Stem Cells; Rectal Fistula; Crohn Disease
PubMed: 37101285
DOI: 10.1186/s13287-023-03331-6 -
Clinical Gastroenterology and... Jun 2024Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and... (Review)
Review
BACKGROUND AND AIMS
Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.
METHODS
We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.
RESULTS
Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.
CONCLUSION
Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
PubMed: 38871152
DOI: 10.1016/j.cgh.2024.05.029 -
Intestinal Research Apr 2022Perianal fistulas are a debilitating manifestation of Crohn's disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management...
BACKGROUND/AIMS
Perianal fistulas are a debilitating manifestation of Crohn's disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD.
METHODS
A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.
RESULTS
A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%-37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%-47.7%) with high heterogeneity (I2=67.1%).
CONCLUSIONS
In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.
PubMed: 35124951
DOI: 10.5217/ir.2021.00091 -
Ultraschall in Der Medizin (Stuttgart,... Jun 2017Transperineal ultrasound (TPUS) is a practical tool for assessing perianal inflammatory lesions. We systematically review its accuracy for detecting and classifying... (Comparative Study)
Comparative Study Meta-Analysis Review
Transperineal ultrasound (TPUS) is a practical tool for assessing perianal inflammatory lesions. We systematically review its accuracy for detecting and classifying perianal fistulae and abscesses. The National Library of Medicine and Embase were searched for articles on TPUS for the assessment of idiopathic and Crohn's perianal fistulae and abscesses. Two reviewers independently reviewed eligible studies and rated them for quality using the QUADAS tool. The primary outcome measure was the accuracy of TPUS as measured by its sensitivity and positive predictive value (PPV) in detecting and classifying perianal fistulae, internal openings and perianal abscesses. We included 12 studies (565 patients). Overall, the methodological quality of the studies was suboptimal. 3 studies were retrospective and 4 showed significant risks of bias in the application of the reference standard. The sensitivity of TPUS in detecting perianal fistulae on a per-lesion basis was 98 % (95 % CI 96 - 100 %) and the PPV was 95 % (95 % CI 90 - 98 %). The detection of internal openings had a sensitivity of 91 % (95 % CI 84 - 97 %) with a PPV of 87 % (95 % CI 76 - 95 %). The classification of fistulae yielded a sensitivity of 92 % (95 % CI 85 - 97 %) and a PPV of 92 % (95 % CI 83 - 98 %). TPUS had a sensitivity of 86 % (95 % CI 67 - 99 %) and PPV of 90 % (95 % CI 76 - 99 %) in the detection of perianal abscesses. The current literature on TPUS illustrates good overall accuracy in the assessment of perianal fistulae and abscesses. However, many studies had methodological flaws suggesting that further research is required.
Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anus Diseases; Child; Child, Preschool; Endosonography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Rectal Fistula; Retrospective Studies; Sensitivity and Specificity; Treatment Outcome; Young Adult
PubMed: 28399604
DOI: 10.1055/s-0043-103954 -
Diagnostics (Basel, Switzerland) May 2023(1) Background: BCC is a sporadic disease that develops in areas of the skin not exposed to the sun. Perianal BCC, which occurs in the anorectal region, accounts for... (Review)
Review
(1) Background: BCC is a sporadic disease that develops in areas of the skin not exposed to the sun. Perianal BCC, which occurs in the anorectal region, accounts for less than 0.2% of all BCC cases. There have been only a few reported cases of the disease, with fewer than 200 cases reported in total. Given the diagnostic challenges and potential for misdiagnosis, we conducted a systematic review of perianal basal cell carcinoma using real-world data to provide comprehensive and detailed information on the disease. (2) Methods: The study was reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2020. Patients' clinical pathologic features, tumor characteristics, treatment modalities, and outcomes were presented. (3) Results: The results of 41 studies involving 140 patients were analyzed. The most common symptoms reported by patients at presentation were anorectal bleeding, pain, and pruritus. Ulceration was the most frequently observed tumor characteristic. The majority of patients underwent local excision as their primary treatment, with only eight patients experiencing a recurrence. Our analysis did not reveal any statistically significant differences in the outcomes of different treatment modalities. (4) Conclusions: Identifying perianal BCC poses a significant challenge as it closely resembles other anal diseases, thereby making it difficult to differentiate between the different conditions. However, a wide local excision with clear margins is considered an effective treatment option for most patients. Alternative treatments, such as radiotherapy, may be recommended for patients who are unable to undergo surgery.
PubMed: 37175041
DOI: 10.3390/diagnostics13091650 -
Journal of Crohn's & Colitis Oct 2016Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and outcomes of older-onset IBD compared with younger-onset subjects.
METHODS
A systematic search of Embase and Medline up to June 2015 identified studies investigating phenotype and outcomes of older-onset [diagnosed at age ≥ 50 years] Crohn's disease [CD] and ulcerative colitis [UC] subjects. Pooled analyses of disease phenotype, medication use, and disease-related surgery were calculated.
RESULTS
We analysed findings from 43 studies comprising 8274 older-onset and 34641 younger-onset IBD subjects. Compared with younger-onset patients, older-onset CD patients were more likely to have colonic disease (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.88 - 3.48) and inflammatory behaviour [OR 1.19, 95% CI 1.07 - 1.33], and less likely to have penetrating disease or perianal involvement. More older-onset UC patients had left-sided colitis [OR 1.49, 95% CI 1.18 - 1.88]. Although fewer older-onset IBD patients received immunomodulators [CD: OR 0.44; UC: OR 0.60] or biologicals [CD: OR 0.34; UC: OR 0.41], older-onset CD was similar in the need for surgery [OR 0.70, 95% CI 0.40 - 1.22] whereas more older-onset UC patients underwent surgery [OR 1.36, 95% CI 1.18 - 1.57].
CONCLUSIONS
Elderly IBD patients present with less complicated disease, but have similar or higher rates of surgery than non-elderly patients. Whether this reflects a non-benign disease course, physicians' reluctance to employ immunomodulators, or both, merits further study which is essential for improving the care of IBD in the elderly.
Topics: Age of Onset; Aged; Aged, 80 and over; Combined Modality Therapy; Disease Progression; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Middle Aged; Models, Statistical; Phenotype; Prognosis
PubMed: 26928965
DOI: 10.1093/ecco-jcc/jjw054 -
Alimentary Pharmacology & Therapeutics Oct 2014The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required. (Review)
Review
BACKGROUND
The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required.
AIM
To review systematically the literature to assess fistula healing rates with medical treatment (anti-TNF-α therapies ± immunomodulators) or surgical treatment alone, compared with combined medical and surgical treatment in fistulising perianal Crohn's disease (CD).
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Two independent reviewers searched the literature.
RESULTS
Twenty-four articles were included. The total population was 1139 patients; 460 (40%) received single treatment with either medical or surgical therapy, and 679 (60%) received combined medical and surgical therapy. Eight studies compared single and combination therapy, with a total population of 797 patients (single therapy: n = 448, combination therapy: n = 349). In the single therapy group, 191/448 were in complete remission (43%). This was lower than the healing rate of the combination therapy group 180/349 (52%). No response to therapy was noted in 34% (153/448) of the single therapy group compared with 23% (80/349) of the combination group.
CONCLUSIONS
Combined surgical and medical (anti-TNF-α ± immunomodulators) therapy may have additional beneficial effects on perianal fistula healing in patients with Crohn's disease, compared with surgery or medical therapy alone. A well-designed Crohn's perianal fistula clinical trial is required in a multidisciplinary medical and surgical setting, with clearly defined end points of clinical (and likely patient reported outcomes) and radiological healing.
Topics: Combined Modality Therapy; Crohn Disease; Humans; Immunologic Factors; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 25115149
DOI: 10.1111/apt.12906 -
Alimentary Pharmacology & Therapeutics Jun 2015It has been reported that thalidomide may be effective in treating inflammatory bowel disease (IBD). (Review)
Review
BACKGROUND
It has been reported that thalidomide may be effective in treating inflammatory bowel disease (IBD).
AIM
To review the evidence examining the efficacy and safety of thalidomide for inducing and maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC).
METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed (1950-August 2014), EMBASE (1984-August 2014), Scopus, and Web of knowledge were searched for randomised controlled trials (RCTs), observational studies and case series. The primary outcomes were induction of remission or response for active IBD or relapse rate for patients in remission and subsequently on thalidomide/analogues for at least 3 months.
RESULTS
Twelve studies (2 RCTs and 10 case series) met the inclusion criteria for inducing remission and included 248 patients (10 with UC, 238 with CD). Only one RCT of paediatric CD achieved high quality scores (remission rate thalidomide: 46%, placebo: 12%; p=0.01). The crude pooled remission rate for thalidomide was 49% and 25% in luminal and perianal CD respectively. For UC, 50% achieved remission and 10% had partial response. One case series reported 21 patients (17 CD, four UC) who maintained remission for 6 months. Many adverse events were reported including sedation (32%) and peripheral neuropathy (20%).
CONCLUSIONS
One high quality RCT showed that thalidomide is effective for inducing remission in paediatric CD. The current evidence is insufficient to support using thalidomide to induce remission in UC or adult CD, or to maintain remission in IBD. Significant adverse events may occur, necessitating discontinuation of thalidomide.
Topics: Adult; Child; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Remission Induction; Thalidomide
PubMed: 25858208
DOI: 10.1111/apt.13181 -
Cancers Mar 2021Perianal fistulizing Crohn's disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn's disease are also at risk of... (Review)
Review
Perianal fistulizing Crohn's disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn's disease are also at risk of perianal fistula-related squamous cell carcinoma (SCC). Cancer arising at the site of a chronic perianal fistula is rare in patients with Crohn's disease and there is a paucity of data regarding its incidence, diagnosis and management. A systematic review of the literature was undertaken using Medline, Embase, Pubmed, Cochrane and Web of Science. Several small series have described sporadic cases with perianal cancer in Crohn's disease. The incidence rate of SCC related to perianal fistula was very low (<1%). Prognosis was poor. Colorectal disease, chronic perianal disease and HPV infection were possible risk factors. Fistula-related carcinoma in CD (Chron's disease) can be very difficult to diagnose. Examination may be limited by pain, strictures and induration of the perianal tissues. HPV is an important risk factor with a particular carcinogenesis mechanism. MRI can help clinicians in diagnosis. Examination under anesthesia is highly recommended when findings, a change in symptoms, or simply long-standing disease in the perineum are present. Future studies are needed to understand the role of HPV vaccination in preventing fistula-related cancer.
PubMed: 33809997
DOI: 10.3390/cancers13061445 -
Inflammatory Bowel Diseases Oct 2022Perianal Crohn's disease (pCD) is a potentially severe phenotype of CD. We conducted a systematic review with meta-analysis to estimate cumulative incidence, risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Perianal Crohn's disease (pCD) is a potentially severe phenotype of CD. We conducted a systematic review with meta-analysis to estimate cumulative incidence, risk factors, and outcomes of pCD in population-based cohort studies.
METHODS
Through a systematic literature review through March 1, 2021, we identified population-based inception cohort studies reporting cumulative incidence of perianal disease (primarily abscess and/or fistula) in patients with CD. We estimated the cumulative incidence of pCD at presentation and 1-, 5-, and 10-year follow-up, and risk factors for perianal disease and outcomes including risk of major (bowel resection, proctectomy, ostomy) and minor perianal (incision and drainage, seton placement, etc.) surgery.
RESULTS
In 12 population-based studies, prevalence of pCD was 18.7% (95% confidence interval [CI], 12.5%-27.0%) with 1-, 5-, and 10-year risk of perianal disease being 14.3% (95% CI, 7.9%-24.6%), 17.6% (95% CI, 11.3%-26.5%), and 18.9% (95% CI, 15.0%-23.4%), respectively. Approximately 11.5% of patients (95% CI, 6.7%-19.0%) had perianal disease at or before CD diagnosis. Colonic disease location and rectal involvement were associated with higher risk of pCD. Overall, 63.3% of patients (95% CI, 53.3-72.3) required minor perianal surgery and 6.4% of patients (95% CI, 1.8%-20.6%) required major abdominal surgery for pCD. Use of biologic therapy for pCD is common and has steadily increased throughout the years.
CONCLUSIONS
Approximately 1 in 5 patients with CD develops perianal disease within 10 years of CD diagnosis, including 11.5% who have perianal disease at presentation. Approximately two-thirds of patients require perianal surgery, with a smaller fraction requiring major abdominal surgery.
Topics: Cohort Studies; Crohn Disease; Humans; Incidence; Proctectomy; Rectal Fistula; Treatment Outcome
PubMed: 34792604
DOI: 10.1093/ibd/izab287